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New biological markers in lymphoproliferative diseases
Špaček, Martin ; Mandys, Václav (advisor) ; Smolej, Lukáš (referee) ; Lysák, Daniel (referee)
New biological markers in lymphoproliferative diseases Summary The prognosis of patients with lymphoid neoplasms is extremely variable. Reliable prognostic markers could allow the identification of patient subsets that may benefit from alternate approaches. Epstein-Barr virus (EBV) is associated with approximately one third of Hodgkin lymphoma (HL) cases. EBV-DNA is often present in the plasma and whole blood of EBV-associated HL patients. However, the significance of EBV-DNA monitoring is debated. In a cohort of 165 adult HL patients EBV-DNA viral load was prospectively monitored. Our results suggest that assessment of plasma EBV-DNA viral load might be of value for estimation of prognosis and follow-up of patients with EBV-positive HL. The role of the TP53 gene's R72P polymorphism in NHL has been analyzed in several studies but it has not been studied in HL. We have evaluated the role of R72P in 340 NHL and 298 HL patients. Our results support the evidence that R72P is not a prognostic factor in Caucasian NHL patients, and they indicate its irrelevance for HL development or prognosis. In a study of 73 patients with chronic lymphocytic leukemia we have assessed IgVH mutational status, presence of mutation in TP53 gene and expression of CD38 and ZAP-70. Overall concordance between ZAP-70 expression and IgVH...
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Prognostic importance of angiopoietin-2 gene transcription in chronic lymphocytic leukemia.
Gradošová, Iveta ; Pecka, Miroslav (advisor) ; Smolej, Lukáš (referee)
Chronic lymphocytic leukemia (CCL) is the most common leukemia, which is characterised by a high variable progress. According to scientific evidence acquired during several last years, angiogenesis has been proven to play an important role in pathogenesis of CLL. One of the very important cytokines playing role in this process is angiopoietin-2 (Ang-2). Elevated expression of Ang-2 has been reported in several hematological malignancies; however, data regarding Ang-2 in CLL are very limited. I measured Ang-2 transcript levels in purified mononuclear cels of 24 untreated patients with CLL by quantitative real-time PCR and normalized them for differences in RNA concentration in each sample by quantitation of transcript of Abl1 housekeeping gene. Elevated Ang-2 mRNA concentrations were detected in 10 cases (Ang-2 to Abl1 expression ratio > 5x10-3). On the other hand, 14 patients had very low or undetectable levels of Ang-2 mRNA (Ang-2 to Abl1 expression ratio < 5x10-3 or Ang-2 Cp > 35). The association between Ang-2 expression and other prognostic factors, clinical stage according to Rai and clinical course of CLL was evaluated by Chi-Square method. There was a significant association between high Ang-2 mRNA levels and unmutated IgVH genes (n= 21, p = 0.012), but not with CD38 (p = 0.057), ZAP-70 expression (p...
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